RESUMO
The efficacy and safety profile of mavacamten, a cardiac myosin inhibitor for the treatment of hypertrophic cardiomyopathy (HCM) is not well-established, prompting the need for an updated meta-analysis. The authors conducted an extensive search across multiple electronic databases, including Embase, MEDLINE (via Pubmed), and CENTRAL, to identify randomized controlled trials (RCTs) assessing the efficacy and safety of mavacamten in HCM. Review Manager 5.4 (Revman) was employed to pool risk ratios (RR) and mean differences (MD). Our literature search yielded 4 RCTs with a total of 503 patients. Mavacamten was found to be associated with higher rates of greater than or equal to 1 New York Heart Association (NYHA) class improvement (RR 2.20, 95% CI: 1.48-3.28; I2=51%) and change from baseline in the Kansas City Cardiomyopathy Questionnaire- Clinical Summary Score (KCCQ-CSS) (MD 7.50, 95% CI: 3.44-11.55; I2 =50%). Mavacamten was also associated with improved resting left ventricular outflow tract (LVOT) gradient (MD -38.33, 95% CI: -49.38 to -27.28; I2 =75%), Valsalva LVOT gradient (MD -48.08, 95% CI: -62.21 to -33.96; I2 =78%), post-exercise LVOT gradient (MD -37.1, 95% CI: -44.37 to -29.84; I2 =0%), LVMI (MD -16.91, 95% CI: -28.29 to -5.54; I2 =88%), and lower rates of septal reduction therapy (SRT) (RR 0.30, 95% CI: 0.22-0.40; I2 =0%). There were no significant differences between mavacamten and placebo regarding the composite functional outcome, greater than or equal to 1 treatment-emergent adverse event, greater than or equal to 1 serious adverse event, and atrial fibrillation. The authors; findings suggest that mavacamten contributes to improvements in NYHA class, KCCQ-CSS scores, and LVOT gradients while reducing the incidence of SRT in patients with HCM.
RESUMO
Celiac disease is an autoimmune disorder characterized by a broad spectrum of histological damage to the intestinal mucosa. Comprehension and understanding of the association between anti-tissue transglutaminase (anti-tTG) antibody levels and the histological severity of celiac disease are not well established, prompting the need for meta-analysis. This study aims to offer insights into the diagnostic abilities of anti-tTG antibody levels in determining the histological severity of celiac disease by providing quantitative evidence based on a diverse range of studies. An extensive search was conducted across four electronic research databases to identify primary research articles reporting serum anti-tTG antibody levels in correlation with different Marsh grades, signifying the histological severity of celiac disease. The software tool RevMan 5.4 (the Cochrane Collaboration, London, UK) was used to compile standardized mean differences (SMD) alongside their respective confidence intervals. A total of 13 studies were included in the meta-analysis, with a patient pool of 2505 patients. Marsh grade I and II were found to have higher anti-tTG antibody levels compared to those with grade 0 (SMD 1.50; 95% CI: 1.12, 1.87; p-value <0.00001). Antibody levels were higher in Marsh grade IIIa when compared to both grade 0 (SMD 0.97; 95% CI: 0.67, 1.28; p-value <0.00001) and grade ≤2 (SMD 0.61; 95% CI: 0.44, 0.79; p-value <0.00001). Patients with Marsh IIIb also reported greater anti-tTG levels compared to grade 0 (SMD 1.48; 95% CI: 0.99, 1.96; p-value <0.00001) and grade ≤2 (SMD 0.98; 95% CI: 0.79, 1.18; p-value <0.00001). Likewise, Marsh grade ≥IIIc reported high levels of anti-tTG antibodies in comparison with grade 0 (SMD 1.06; 95% CI: 0.72, 1.39; p-value <0.00001) and grade ≤2 (SMD 1.18; 95% CI: 1.02, 1.34; p-value <0.00001). Our meta-analysis revealed a consistent, robust correlation between anti-tTG antibody levels and the histological severity of celiac disease, with a clear trend of increasing antibody levels corresponding to the severity of mucosal damage. Large-scale primary research initiatives are needed to reach definitive conclusions.